Why do some people never seem to get sick and others always?

A study in tadpoles revealed that there are some mechanisms capable of allowing greater tolerance to diseases.

Madrid, June 20 (Europa Press).- Why do some people never seem to get sick while others are constantly victims of viruses and bacteria? How can the partner of a sick person avoid getting infected despite sleeping next to her every night? Questions like these have become top of mind for many people during the COVID-19 pandemic, and scientists are now a giant step closer to answering them thanks to aquatic helpers: tadpoles.

    Researchers at Harvard University's Wyss Institute for Biologically Inspired Engineering have discovered genetic and biological mechanisms that enhance disease tolerance (the ability of cells and tissues to resist damage in the presence of invading pathogens). ) in developing tadpoles of frogs Xenopus laevis, and have identified drugs that can keep the tadpoles alive even in the presence of lethal bacteria.

Many of the same mechanisms are found in mammals as well, suggesting that infections in humans and other animals could one day be treated by increasing their tolerance to pathogens.

    “The standard approach to treating infections for the past 75 years has been to focus on killing the pathogen, but the overuse of antibiotics in livestock and in humans has led to the emergence of antibiotic-resistant bacteria that are costing us more and more. more kill. Our research has shown that focusing on modifying the host response to a pathogen, rather than killing the pathogen itself, could be an effective way to prevent death and illness without exacerbating the problem of antibiotic resistance." Megan Sperry, first author of the study, which has been published in the scientific journal Advanced Science.

The phenomenon of tolerance of some hosts to infectious pathogens that should make them sick has been well documented by science in recent decades. Mice, for example, can harbor the pneumonia-causing Pneumococcus bacteria in their nostrils without showing signs of illness, and African and Asian monkeys are known to be less susceptible to certain pathogens than humans and our close ape relatives .

Research into the biology of disease tolerance has found that it is associated with the activation of stress responses that are normally induced by low oxygen (hypoxia). These cellular responses reprogram T cells, reducing the amount of inflammation they cause, and also influence the movement of metal ions, which are crucial for the survival of bacteria.

Sperry and his team wanted to see if they could use a combination of computational techniques and hands-on experiments to decipher the genes and molecular pathways that control tolerance in Xenopus frogs, and then find existing drugs that could activate those pathways and induce a state of tolerance. against pathogens.